The overall goal of this P50 application is to support a highly multidisciplinary team of imaging scientists, chemists, biologists, and physicians to develop and rapidly translate new molecular imaging approaches to better diagnose, understand and treat cancer. The current team includes investigators from Massachusetts General Hospital (MGH), Dana Farber Cancer Institute, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School (HMS), Harvard University (HU), Massachusetts Institute of Technology (MIT) and the new MIT/Harvard Broad Institute. The Program is affiliated with two NCI designated Cancer Centers: the Dana Farber Harvard Cancer Center (DFHCC) and the MIT Center for Cancer Research (CCR). Project 1 (Weissleder, Schreiber) will develop libraries of imaging agents for the rapid discovery of prostate cancer. Project 2 (Josephson, Cantley, Verdine) will develop novel approaches to image kinases (P13K, Akt) that play a key role in signal transduction and have potential for imaging therapeutic intervention upstream. Project 3 (Breakefield, Sena-Estevez) will develop novel tools to ask critical questions about neuroprecursor cells and glioma treatment. Project 4 (Pittet, von Andrian, Scadden) will apply novel imaging tools to elucidate the role of T-cells in tumor killing. A major goal of this application is to train a cadre of young investigators in the use and application of molecular imaging tools. Multidisciplinary training will involve participation in hands-on projects, seminars, didactic lecture series and funded pilot projects. A dedicated Mouse Core is in place to allow broad access to imaging in relevant cancer models in a cost-effective way, to facilitate rapid translational development and to test the in vivo distribution and efficacy of novel imaging probes. A Chemistry Core is in place to provide custom synthesized imaging probes, to scale up syntheses and develop cost-effective imaging agents. This established Center has a proven track record for innovation in molecular imaging and clinical translation and is poised to attack fundamental issues in cancer through the use of new technologies.